anxiolytics & sedatives Flashcards
barbituates
1st class of drugs developed to tx anxiety- mostly replaced by benzodiazepines
- both drug classes are noted for dependency, both psychological & physical
- CNS depressants=> calming effect, sleep, anesthesia, coma, death
- NO ANALGESIC effect!
- classified by the length of acton
- severe withdrawl ssx- s/t fatal
receptor sites for barbs & benzos
-adjacent to GABA site on cell membranes of CNS neurons- increases the affinity of the GABA receptor for GABA= prolonged opening of the CL channels= dec firing opportunity for that neuron
(dec in GABA funx assoc. w/seizures)
ultra short acting barbituates
- produce anesthesia w/in 1 min of IV admin
- thiopental/ pentothal- known as “truth serum”, really just disinhibits people, if you don’t want to say something you won’t
short acting barbituates
- oral doses produce effects w/in approx. 15-30min, duration of 6-8hrs
- pentobarbital/ nembutal
intermediate acting barbituates
- oral admin = 20-40min onset of action, lasts up to 6hs
* butalbital/ fiorinal
long acting barbituates
- effect realized in about 1hr, lasts for about 12hrs
- primarily used to tx seizure DO
- phenobarbital/ luminal
phenobarbital/ luminal
- most widely used anti-convulsant worldwide
- oldest seizure med still commonly used
- sedative & hypnotic properties- has be replaced by benzodiazepines for this indication
benzodiazepines
- most widely used group of anxiolytic drugs
- bind to with high affinity to receptors adjacent to GABA receptors, on cell membrane of CNS- inhances affinity of GABA receptors for endogenous GABA
- opens CL channels= hyperpolarization of neuronal membrane= more difficult to depolarize the nerve cell
short acting-benzodiazepines
-generally used for pts with sleep onset insomnia
midazolam/ versed
Short acting benzodiazepine
For sedation & anxiety prior to upper GI endoscopy or prior to anesthesia
-potent sedative, hypnotic, anxiolytic, anticonvulsant, skeletal muscle relaxant, amnestic properties
-usu IV, but also syrup for pediatric
-acute management of aggressive, violent or delirious pts
-long-term use for seizure DO is not recommended- development of tolerance, and marked sedation effect
long acting benzodiazepines
longer duration of action
for tx of insomnia & anxiety
**esp for tx of seizure DO
Examples of long acting benzodiazepines
- Clonazepam/Klonopin
- Diazepam/ Valium
- Clorazepate/ Tranxene
Diazepam/ valium
long acting benzodiaepine
used as an anxiolytic, sedative, muscle relaxant, seizure control
MOA- binds to benzodiazepine receptors in CNS- enhances GABA activity
-PO, PR, IV- metabolized in liver to active metabolites, prolongs duration
SE- drowsiness, impaired mentation, tolerance & addiciton. rebound insomnia after discontinuation
**severe withdrawl possible(fatal)
-tx for insomnia has been largely replaced with shorter acting benzo’s
benzodiazepine like sedatives
zolpidem/ ambien
zaleplon/sonata
eszopiclone/lunesta
- act to increase GABA receptor affinity for endogenous GABA- do not act on benzo or barb receptor sites
zolpidem/ambien
short acting non-benzodiazepine hyponotic
for insomnia
potentiates GABA by binding to GABAa receptors- same location as benzo receptors
works quickly(w/in 15min) w/short half life(2-3hrs)
-does not effectively maintain sleep
eszopiclone/lunesta
benzodiazepine-like hypnotic
for insomnia
potentiation of GABA effect on Cl ion channels- does not bind to benzo receptors
PO- rapid onset(15-30min), no evidence of tolerance
SE- impaired mentation prior to sedation, minimal drowsiness upon waking, minimal chx in mentation compared to other benzo’s full side effect profile may not be apparent until 5yr duration of use
ramelteon/rozerem
melatonin agonist- sedative hypnotic
for insomnia?
MOA- melatonin receptor agonist, high affinity to melatonin MT1 & MT2 receptors- mimics & enhances the action of endogenous melatonin- associated with maintenance of circadian rhythm
-has shown no measurable affinity to other systems/receptors/transporters/enzymes
-no published studies of effectiveness compared to melatonin supplementation
-available w/out prescription
benzodiazepine withdrawl
cluster of ssx that appear when a person who has developed dependence severely reduces/stops intake
- can provoke life threatening symptms. ie. seizures
- rapid onset of ssx with higher dose/longer dependence removal
benzodiazepine OD
rare by itself
combined intake with alcohol, barbituates, opioids may cause coma or death
common ssx- CNS depression, signs of intoxication- impaired balance, ataxia, slurred speech
-antidote- flumazenil/romazicon
flumazenil/ romazicon
benzodiazepine receptor antagonist
rapidly reverses the effect of benzodiazepines
IV admin only
-rapid onset(1-2min), short half life(1hr)- requires multiple doses to maintain reversal of benzo(esp with OD on long acting benzo’s)
-effective at reversing CNS depression, not so much for respiratory depression
-may cause withdrawal ssx in dependent pts- can cause seizures
